The Moderating Effect of the APOE ε4 Allele on the Relationship Between Hippocampal Volume and Cognitive Decline in Older Depressed Patients

Objective: The apolipoprotein E epsilon-4 (APOE epsilon 4) allele and depression are independently associated with increased risk for cognitive decline (CD). The authors have reported that depressed elders with an APOE epsilon 4 allele had greater CD compared with depressed elders without the allele. Depression affects the hippocampus, and reduced hippocampal volume has been associated with CD. This study sought to examine in depressed patients the relationships between hippocampal volume, the APOE epsilon 4 allele, and their interaction on CD. Analyses were performed to examine the influence of baseline hippocampal volume, the APOE epsilon 4 allele, and their interactions on change in cognitive functioning overtime. Design: Secondary data analysis using linear regression analyses. Setting: Clinical Research Center for the Study of Depression in Later Life conducted at Duke University. Participants: Depressed older patients (N = 61) followed up for 4 years. Measures: At baseline, cognitive functioning (assessed by the Mini-Mental State Examination), left and right hippocampal volume (assessed by magnetic resonance imaging), and APOE genotype were obtained. At 4-year follow-up, cognitive functioning was reassessed. Results: The APOE epsilon 4 allele and left hippocampal volume, but not right hippocampal volume, were independently associated with CD. Importantly, the authors found the APOE epsilon 4 allele to moderate the effects of left hippocampal volume on CD. The APOE epsilon 4 allele seemed to have little effect among those with larger left hippocampal volumes, whereas the allele influenced CD among those with smaller hippocampal volumes. Conclusion: Future studies of cognitive impairment and decline should examine both individual and conjoint effects of putative risk factors. (Am J Geriatr Psychiatry 2010; 19: 23-32)